Epigenetic and transcriptional mechanisms for the regulation of IL-10

IL-10 is a critical immunoregulatory cytokine expressed in virtually all immune cell types. Maintaining a delicate balance between effective immune response and tolerance requires meticulous and dynamic control of IL-10 expression both epigenetically and transcriptionally. In this Review, we describe the epigenetic mechanisms controlling IL-10 expression, including chromatin remodeling, 3D chromatin loops, histone modification and DNA methylation. We discuss the role of transcription factors in directing chromatin modifications, with a special highlight on the emerging concept of pioneer transcription factors in setting up the chromatin landscape in T helper cells for IL-10 induction. Besides summarizing the recent progress on transcriptional regulation in specialized IL-10 producers such as type 1 regulatory T cells, regulatory B cells and regulatory innate lymphoid cells, we also discuss common transcriptional mechanisms for IL-10 regulation that are shared with other IL-10 producing cells.